Heparin is a mixture of sulfated mucopolysaccharides of animal origin which is used in particular for its anticoagulant and antithrombotic properties.
Heparin nevertheless has disadvantages which limit the conditions for its use. In particular, its high anticoagulant activity (anti-IIa activity) can cause hemorrhages.
Low-molecular-weight heparins obtained by basic depolymerization of heparin esters have been proposed (EP40144); however, these products still have a high anti-IIa (aIIa) activity.
Very-low-molecular-weight heparins have also been described in U.S. Pat. No. 6,384,021. However, the anti-Xa (aXa) activity values obtained in the examples described do not exceed 120 IU, and the anti-Xa/anti-IIa ratio obtained is between 15 and 50.
In WO-0208295, very-low-molecular-weight heparins are prepared by a method different from that of U.S. Pat. No. 6,384,021 and exhibit an activity between 100 and 150 IU, with anti-Xa/anti-IIa ratios which are also very high for certain examples of application.
A constant need however exists in this class of medicament to improve the anti-Xa activities, in particular, in obtaining activities greater than 150 IU/mg, as well as the anti-Xa/anti-IIa ratio; and therefore to develop novel generations of heparin derivatives.